# Drug-eluting joint implants with synergistic antimicrobial release and risk stratified models of preclinical efficacy testing

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $364,184

## Abstract

Project Summary/Abstract
There is a fundamental gap in understanding the effect of local delivery of antibiotics for the prevention and
treatment of peri-prosthetic joint infections, a truly morbid and costly complication threatening >1 million
patients undergoing joint arthroplasty each year. There is currently no fully load-bearing medical device which
can also be used for the controlled release of antibiotics to treat peri-prosthetic joint infection (PJI). The current
standard of treatment (there is none for prevention) involves a two-stage revision during which patients are
immobilized for more than 3 months. Available treatments are effective only about 40-80% of the time with
recurrence increasing morbidity, mortality and cost tremendously. There is a great need to improve outcomes,
patients’ quality of life and to reduce cost.
Our long-term goal is to develop materials and methods to enable and thoughtfully control the local release of
therapeutics to treat orthopaedic conditions. The overall objective of this application is to devise an antibiotic-
eluting and load-bearing joint implant platform technology and its implementation strategy to improve the
treatment of PJI. Our central hypothesis is that by manipulating the synergy of incorporated drugs,
drug/polymer interactions and drug incorporation methods, an ultrahigh molecular weight polyethylene
(UHMWPE) implant with optimal antibiotic efficiency and safety can be designed. The rationale for the
proposed research is that by using a newly discovered antibiotic synergy between local PJI antibiotics and
commonly used analgesics, we can optimize drug elution profiles with maximum efficacy in preventing the
growth of clinically relevant infections of variable risk. This strategy has the potential of changing the treatment
paradigms for improved outcomes without any additional risks to patients. The specific aims are (1) identifying
the factors in engineering UHMWPE with synergistic antibacterial release and (2) developing preclinical risk-
stratification tests for the implementation of antibiotic-eluting UHMWPE. The challenge of developing a tough,
fully load-bearing and wear resistant surface while incorporating drugs in the polymer will be overcome by two
strategies: introducing highly eccentric drug clusters that enable lower drug loading and spatially limiting the
drug-loaded regions to low load bearing regions of the implant. The approach is innovative firstly because it
departs from the current methods of depending on antibiotic elution from temporary, non-weight bearing bone
cement devices often assembled in the operating room and secondly because analgesics, which can improve
the efficacy of antibiotics, can be delivered concurrently at a predetermined rate using this device. The
expected outcome is a platform bearing surface technology and an implementation strategy tailored to the
infecting microorganism. The strategies capitalize on the team’s expertise in the development of cli...

## Key facts

- **NIH application ID:** 10127583
- **Project number:** 5R01AR077023-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ebru Oral
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,184
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127583

## Citation

> US National Institutes of Health, RePORTER application 10127583, Drug-eluting joint implants with synergistic antimicrobial release and risk stratified models of preclinical efficacy testing (5R01AR077023-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10127583. Licensed CC0.

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